Evinacumab for Homozygous Familial Hypercholesterolemia

RCT (n=65) reported IV infusion of evinacumab (15 mg/kg) every 4 weeks lowered LDL cholesterol from baseline significantly compared to placebo at week 24 (relative reduction 47.1% vs. increase of 1.9%; between-group least-squares mean absolute difference, –3.4 mmol/L, p<0.001).

SPS commentary:

According to an editorial, the results of this trial of a monoclonal antibody against angiopoietin-like 3 (ANGPTL3) are great news for patients with homozygous familial hypercholesterolemia and may reduce the need for invasive treatment such as apheresis in some patients. It notes that the question then arises as to whether patients without familial hypercholesterolemia who have elevated plasma LDL cholesterol levels may benefit from such therapy. It suggests that for such patients, evinacumab may become of interest if statins, cholesterol-absorption inhibitors, and PCSK9 inhibitors do not lower LDL cholesterol levels to a sufficient degree or have unacceptable side effects. It adds that since evinacumab also substantially lowered plasma triglyceride levels (secondary outcome), the drug may also be useful in patients with familial chylomicronemia syndrome. Although the trial was not designed to assess the effect of evinacumab on cardiovascular risk, it is of the opinon that the large reduction in LDL cholesterol levels in the evinacumab group would be expected to reduce the risk of such clinical outcomes. It concludes that 20 years after the identification of angiopoietin-like proteins, these hormones have fulfilled their promise as targets for lipid-lowering therapy.


New England Journal of Medicine

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